Early antiretroviral therapy (ART) is highly acceptable to the majority of young women with HIV in South Africa, according to research. Rates of virological suppression remained at over 85% regardless of CD4 threshold for starting treatment, and answers to a questionnaire showed that over three-quarters of participants were willing to start treatment when their CD4 count was above 500 cells/mm3. Moreover, half of patients who said they would not consider early treatment actually started therapy with a high CD4 count.
“We found that CD4 counts at ART initiation have been dramatically increasing over the last decade, and that concurrently, HIV viral loads have decreased, potentially having an important impact on HIV transmission at the individual and community level,” comment the authors. “Importantly, while women started ART earlier, this did not have a negative impact on adherence, as demonstrated by similar rates of virological suppression up to two years post-ART initiation regardless of the CD4 count at treatment start.”
In 2015 the World Health Organisation (WHO) issued updated guidelines recommending immediate ART for all HIV-positive individuals, regardless of CD4 count. The benefits of early treatment are now well established, including a reduced risk of HIV- and non-HIV-related illness and a low risk of onward transmission of the virus.
Despite these benefits, concerns have been voiced that patients in good health with a high CD4 count may not see the value of early treatment and therefore be reluctant to start treatment. There are also concerns that people in this group would have poor adherence, even if they started treatment.
Investigators from the ongoing South African CAPRISA 002 cohort – the Centre for the AIDS Programme of Research in South Africa (CAPRISA), Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal and the department of epidemiology, Columbia University, New York City – therefore designed a study describing trends in CD4 count at ART initiation according to WHO and national guidelines; to determine rates of viral suppression after ART initiation at different CD4 levels; and using a questionnaire, to assess the perceived benefits and acceptability of early ART.
The study population consisted of 232 women living with HIV, who had not previously taken HIV treatment, recruited between 2006 and 2015. The first women started therapy in 2006 when the CD4 cell threshold for the initiation of ART was 200 cells/mm3. This increased to 350 cells/mm3 in 2013 and to 500 cells/mm3 in 2015. Universal therapy, regardless of CD4 cell count, was recommended in 2016.
Study participants were followed 1, 3, 6 and 12 months after ART initiation and at intervals of six months thereafter. Viral suppression was defined as a viral load below 400 copies/ml.
A subset of 51 women who received care in 2014-15 completed a questionnaire about the acceptability of early ART. Just over two-thirds (68%) of participants started ART between January 2006 and December 2015. Mean CD4 count at ART initiation was 217 cells/mm3 before 2010, increasing to 531 cells/mm3 in 2015. Mean viral load simultaneously decreased from 158,000 copies/ml to 12,600 copies/ml.
Rates of viral suppression at 3, 6, 12 and 18 months after ART initiation were analysed. At least 86% of patients had an undetectable viral load at all time points. There was no significant difference between rates of suppression according to whether therapy was initiated at the CD4 thresholds of 350 or 500 cells/mm3.
The 51 participants who completed the questionnaire had a median age of 28 years. Their mean CD4 count was 590 cells/mm3 and median viral load approximately 12,600 copies/ml.
Participants recognised the health benefits of early ART, including a reduced risk of TB (94%), reduced risk of illness and death (92%), reduced risk of organ disease (84%), a reduction in the risk of HIV transmission during pregnancy and breastfeeding (90% and 84%) and a reduced risk of HIV transmission to a sexual partner (88%).
However, some participants were concerned about treatment side-effects (59%), the need to take life-long therapy (37%), daily therapy (35%), having to disclose HIV status because of treatment (57%) and a fear of stigma (57%).
Overall, 78% of women were willing to start ART while their CD4 count was above 500 cells/mm3. Of those, 70% said they felt ready to start treatment, with 90% stating this was to improve their health, and 30% citing the desire the start a family.
Of the 22% of women who said they were unwilling to start early treatment, 91% stated this was because they felt well and therefore did not perceive a need for ART. Other reasons included concerns about side-effects (46%), taking a large number of pills (27%) and having to disclose HIV infection status to a partner (27%).
Most of the participants (94%) had a current partner. Just over half (55%) knew the HIV status of their partner, with 82% of these reporting their partner was HIV-positive. However, only 23% had a partner who was taking ART.
Just over two-thirds of participants started ART within six months of completing the questionnaire. This included 73% of women who said they would be willing to consider early ART; these patients had a mean CD4 count of 717 cells/mm3 at treatment initiation. Half the women who indicated they did not want to start early ART did in fact start therapy; their mean CD4 count was 690 cells/mm3. Just under a third (31%) did not start treatment, with a mean CD4 count of 815 cells/mm3.
The investigators acknowledge that as their study population consisted of young women, the findings may not be generalizable to other populations. Other possible limitations include high levels of ART awareness among their cohort and the small sample size.
Despite this, the authors conclude that ART initiation at higher CD4 counts is acceptable and feasible.
WHO guidelines recommend immediate initiation of antiretroviral therapy (ART) for all individuals at HIV diagnosis regardless of CD4 count, but concerns remain about potential low uptake or poor adherence among healthy patients with high CD4 counts, especially in resource-limited settings. This study assessed the acceptability of earlier treatment among HIV-positive South African women, median age at enrollment 25 (IQR 22–30), in a 10 year prospective cohort study by (i) describing temporal CD4 count trends at initiation in relation to WHO guidance, (ii) virological suppression rates post-ART initiation at different CD4 count thresholds, and (iii) administration of a standardized questionnaire. 158/232 (68.1%) participants initiated ART between 2006 and 2015. Mean CD4 count at initiation was 217 cells/µl (range 135-372) before 2010, and increased to 531 cells/µl (range 272–1095) by 2015 (p < 0.001). Median viral load at ART initiation decreased over this period from 5.2 (IQR 4.6–5.6) to 4.1 (IQR 3.4–4.6) log copies/ml (p = 0.004). Virological suppression rates at 3, 6, 12 and 18 months were consistently above 85% with no statistically significant differences for participants starting ART at different CD4 count thresholds. A questionnaire assessing uptake of early ART amongst ART-naïve women, median age 28 (IQR 24–33), revealed that 40/51 (78.4%) were willing to start ART at CD4 ≥500. Of those unwilling, 6/11 (54.5%) started ART within 6 months of questionnaire administration. Temporal increases in CD4 counts, comparable virological suppression rates, and positive patient perceptions confirm high acceptability of earlier ART initiation for the majority of patients.
Nigel Garrett, Emily Norman, Kerry Leask, Nivashnee Naicker, Villeshni Asari, Nelisile Majola, Quarraisha Abdool Karim, Salim S Abdool Karim